4-64280129-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001010874.5(TECRL):c.1035G>A(p.Leu345=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,603,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
TECRL
NM_001010874.5 synonymous
NM_001010874.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.65
Genes affected
TECRL (HGNC:27365): (trans-2,3-enoyl-CoA reductase like) The protein encoded by this gene contains a ubiquitin-like domain in the N-terminal region, three transmembrane segments and a C-terminal 3-oxo-5-alpha steroid 4-dehydrogenase domain. The protein belongs to the steroid 5-alpha reductase family. Mutations in this gene result in ventricular tachycardia, catecholaminergic polymorphic, 3. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 4-64280129-C-T is Benign according to our data. Variant chr4-64280129-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1772382.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.65 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECRL | NM_001010874.5 | c.1035G>A | p.Leu345= | synonymous_variant | 12/12 | ENST00000381210.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECRL | ENST00000381210.8 | c.1035G>A | p.Leu345= | synonymous_variant | 12/12 | 1 | NM_001010874.5 | P1 | |
TECRL | ENST00000511997.1 | c.*50G>A | 3_prime_UTR_variant | 2/2 | 1 | ||||
TECRL | ENST00000507440.5 | c.964+912G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151864Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 244968Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 132944
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1451690Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2AN XY: 721948
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 151982Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74276
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at